Compositions and methods for inhibiting protein on surfaces

ABSTRACT

The use of NIPAM polymers to prevent or reduce the formation of protein deposits on the surfaces of medical devices is described. The invention is particularly directed to reduction of the adsorption of proteins on surfaces of contact lenses and other medical prosthetics.

BACKGROUND OF INVENTION

[0001] The present invention is directed to the reduction of proteindeposition on surfaces. The invention provides compositions and methodsfor inhibiting the deposition of protein on the surfaces of medicaldevices, particularly biomedical and prosthetic devices. The inventionis based on the discovery that certain polymers and related copolymerscomprising the monomer n-isopropylacrylamide (NIPAM) significantlyinhibit protein deposition on the surfaces of contact lenses.

[0002] Proteins adsorb to almost all surfaces and the minimization orelimination of protein adsorption has been the subject of numerousstudies, such as those reported by Lee, et al., in J. Biomed. MaterialsRes., vol. 23, pages 351-368 (1989). Sensors, chromatographic supports,immunoassays, membranes for separation, biomedical implants, prostheticdevices (e.g., contact lenses) and many other devices or objects can beadversely affected by protein adsorption. A method and/or means fortreating the surfaces of such objects so as to prevent or reduce proteindeposition would therefore be quite advantageous.

[0003] The use of NIPAM-containing polymers to modify surfaces andcontrol protein deposition on glass and silicon substrates has beenpreviously described. The following publications provide furtherbackground regarding such modifications:

[0004] 1. Kidoki, et al., Langmuir, 17, pp. 2402-2407 (2001);

[0005] 2. Bohanon, et al., J. Biomater. Sci. Polymer Edn., Vol. 8, No.1, pp.19-39 (1996);

[0006] 3. International (PCT) Patent Publication No. WO 02/30571 A2(Sudor);

[0007] 4. U.S. Pat. No. 6,447,897 (Liang, et al.);

[0008] 5. U.S. Pat. No. 6,270,903 (Feng, et al.); and 6. Huber, et al.,Science, Vol. 301, pp. 352-354, Jul. 18, 2003.

[0009] The above-identified publications do not disclose or suggest thatNIPAM-containing polymers could be used to modify the surfaces ofmedical devices, such as contact lenses, and to control proteindeposition and release on such surfaces.

[0010] The terms “soft” and “hard” relative to contact lenses aregenerally associated with not only the relative hardness of therespective types of lenses, but also the type of polymeric material fromwhich the lenses are formed. The term “soft” generally denotes a contactlens that is formed from a hydrophilic polymeric material, such ashydroxyethyl methacrylate or “HEMA”, while the term “hard” generallydenotes a lens that is formed from a hydrophobic polymeric material,such as polymethylmethacrylate or “PMMA”. The surface chemistry andporosity of the hard and soft lenses is quite different. Soft lensestypically contain a large amount of water, are quite porous, and bearionic charges on the exposed surfaces of the lenses, while hard lensesare considerably less porous and generally do not bear ionic surfacecharges.

[0011] The ionic surfaces and porous nature of soft contact lenses canlead to significant problems when the lenses come into contact with thetear film due to the complex composition of the tear film, which islargely comprised of proteins, lipids, enzymes and various electrolytes.Tear components include albumin, lactoferrin, lysozyme and a number ofimmunoglobulins. The uptake of proteins from the tear fluid onto thelens is a common problem and depends on a number of factors, includingthe nature of the materials from which the lens is made.

[0012] Soft contact lenses act as efficient substrates for proteindeposition and adsorption. This fouling can lead to dehydration of thelens and instability of the tear film, resulting in discomfort and lackof tolerance in the wearer. Adsorption of proteins can also facilitatebacterial colonization and this can increase the risk ofvision-threatening infections.

[0013] In view of the potential fouling of contact lenses and theproblems created by such fouling, as discussed above, it is generallyaccepted that contact lens cleaning must be a regular part of apatient's lens care regimen. Many different types of cleaning agentshave been utilized in the past for this purpose. Cleaning agents such assurfactants and enzymes are typically incorporated into contact lenscare products to remove protein deposits. However, the use of theseagents can lead to irritation, and in cases where rubbing and cleaningregimens are required, there is a possibility that the cleaning agentswill not be used properly or will be used in a manner that damages thelenses. In view of the foregoing problems, it would be advantageous ifthe surfaces of contact lenses could be modified so as to prevent orreduce the adsorption of proteins to the surfaces.

[0014] Various attempts have been made to reduce protein depositformation on s contact lenses. The following patents may be referred tofor further background regarding such attempts:

[0015] U.S. Pat. No. 4,411,932 describes the use of polymeric alcoholsand polymeric ethers, including poly(ethylene glycol), polyethyleneoxide and polyethylene glycol methyl ether, as prophylactic agentsagainst soilant deposits on contact lenses;

[0016] U.S. Pat. No. 6,274,133 (Hu et al.) describes the use of cationiccellulose polymers to prevent the build-up of lipids and proteins on asilicone-hydrogel lens;

[0017] U.S. Pat. No. 6,323,165 (Heiler, et al.) describes the use ofcharged polyquaternium polymers to block the binding of proteins tohydrophilic contact lenses; and

[0018] U.S. Pat. No. 6,096,138 (Heiler, et al.) describes the use ofpolyquaternium polymers such as Luviquate (BASF), which is a mixture ofvinylpyrrolidone and vinylimidazolium moieties that can bind tohydrophilic contact lens materials, so as to block the binding ofproteinaceous materials to the lenses.

[0019] These prior attempts to reduce protein binding have drawbacks.For example, cationic polymers may act as irritants upon contact withthe eye when utilized at high concentrations. Additionally, due to thepositive charge character of these macromolecules, complex formationwith anionic surfactants or other components of CLC products may lead toflocculation and phase separation in the formulation, which is asignificant problem. Accordingly, there is need for new approaches toprovide protein resistant surfaces.

[0020] Due to the trend toward use of extended wear lenses, it would beuseful to be able to provide contact lens wearers with a contact lenssurface that inhibits adsorption of proteinaceous matter for extendedtime periods, without compromising the safety of the patient. Thepolymer should also be compatible in contact lens care solutions whenstorage, disinfection and/or cleaning are desired by the patient. Thepresent invention is directed to satisfying these needs.

SUMMARY OF INVENTION

[0021] The present invention is directed to the use of polymers that aresurface active and exhibit a temperature response in aqueous solutions.The polymers and related polymers (e.g., co-polymers) are formed from aN-isopropylacrylamide (“NIPAM”) monomer.

[0022] The present invention is based on a discovery that the NIPAMpolymers and related polymers may be utilized to inhibit proteindeposition on the surfaces of hydrogel contact lenses. The NIPAMpolymers provide unique solution properties, and it has been discoveredthat these properties can be employed in formulations where proteinresistant hydrogel surfaces are desired.

[0023] As discussed above, there is a need for improved approaches formodifying the adsorption of proteins on the surfaces of contact lenses.The present invention is based on a discovery that the NIPAM polymersdescribed herein are uniquely suited for this purpose.

[0024] The NIPAM polymers described herein may be employed in variousmanners in order to achieve modification of contact lens surfaces andsurfaces of other medical devices. For example, contact lenses can bestored in solutions containing NIPAM polymers prior to being worn. Thisprophylactic approach allows the polymers to form a protective layer onthe surface of the lenses before the consumer even exposes the lenses totear fluids containing protein. The NIPAM polymers may also beincorporated in multi-purpose solutions for treating contact lenses on adaily basis. Chemical grafting on surfaces to form permanent coatings ofNIPAM polymers is another method for preparing protein resistantsurfaces.

[0025] In addition to contact lenses, the surface modificationtechniques described herein may be applied to various medical deviceswhere protein resistant surfaces are desired, such as intraocularlenses, catheters, cardiac stents, prosthetics, and other medicaldevices that undergo prolonged exposure to proteins during use in or onthe bodies of humans or other mammals.

[0026] Although not wishing to be bound by theory it is believed thatthe NIPAM polymers described herein have a range of inherent physicalproperties (e.g., low interfacial free energy, hydrophilic-hydrophobicproperties, very low toxicity, dynamic surface mobility and stericstabilization) that enable these polymers to exhibit superior proteininhibiting characteristics.

BRIEF DESCRIPTION OF DRAWINGS

[0027]FIG. 1 is a graph showing the results of the tests described inExample 1; and

[0028]FIG. 2 is a graph showing the results of the tests described inExample 3.

DETAILED DESCRIPTION OF THE INVENTION

[0029] The NIPAM polymers utilized in the present invention have thefollowing formula:

[0030] wherein n is a whole number of from 10 to 3,000.

[0031] The NIPAM polymers utilized in the present invention includevarious types of polymers that comprise the above-described monomer. Thepolymers may be formed entirely from the NIPAM monomer identified above,or other monomers can be incorporated into the polymer by copolymerizingthe NIPAM monomer with other monomers, such as acrylic acid, acrylamide,N-acetylacylamide, N, N-dimethylacrylamide and butyl methacrylate. Inaddition, modified polymers or copolymers containing the NIPAM monomercan be prepared by functionalization of end groups, preparation of blockcopolymers, and cross-linking of polymers. All such polymers, copolymersor modifications thereof are referred to herein as either “NIPAMpolymers” or “PNIPAM”. The NIPAM polymers utilized in the presentinvention will typically have molecular weights of from 1,000 to 300,000Daltons. The polymers are available from Polymer Source, Inc., Dorval,Quebec (Canada).

[0032] The amount of PNIPAM utilized in the compositions of the presentinvention will vary depending on the form of the compositions and theintended use thereof. The concentration of PNIPAM utilized willgenerally be an amount sufficient to obtain a solution surface tensionof less than 50 milliNewtons per meter (“mNm⁻¹”) at room temperature(23° C.).

[0033] The above-described NIPAM polymers are surface active, andtherefore will readily adsorb to most types of surfaces. Factors such asthe type of surface (hydrophobic versus hydrophilic), temperature,buffer and excipients will influence the interaction between thepolymers and a surface, and will influence the magnitude of theinteractions.

[0034] The above-described PNIPAM polymers may be combined with othercomponents commonly utilized in products for treating contact lenses,such as rheology modifiers, enzymes, antimicrobial agents, surfactants,chelating agents or combinations thereof. The preferred surfactantsinclude anionic surfactants, such as RLM 100, and nonionic surfactants,such as the poloxamines available under the name “Tetronic®”, and thepoloxamers available under the name “Pluronic®”. Furthermore, a varietyof buffering agents may be added, such as sodium borate, boric acid,sodium citrate, citric acid, sodium bicarbonate, phosphate buffers andcombinations thereof.

[0035] The compositions of the present invention that are intended foruse as CLC products will contain one or more ophthalmically acceptableantimicrobial agents in an amount effective to prevent microbialcontamination of the compositions (referred to herein as “an amounteffective to preserve”), or in an amount effective to disinfect contactlenses by substantially reducing the number of viable microorganismspresent on the lenses (referred to herein as “an amount effective todisinfect”).

[0036] The levels of antimicrobial activity required to preserveophthalmic compositions from microbial contamination or to disinfectcontact lenses are well known to those skilled in the art, based both onpersonal experience and official, published standards, such as those setforth in the United States Pharmacopoeia (“USP”) and similarpublications in other countries.

[0037] The invention is not limited relative to the types ofantimicrobial agents that may be utilized. Examples of antimicrobialagents that may be used include: chlorhexidine, polyhexamethylenebiguanide polymers (“PHMB”), polyquaternium-1, and the amino biguanidesdescribed in co-pending U.S. patent application Ser. No. 09/581,952 andcorresponding International (PCT) Publication No. WO 99/32158, theentire contents of which are hereby incorporated in the presentspecification by reference.

[0038] The preferred antimicrobial agents are polyquaternium-1, andamino biguanides of the type described in U.S. patent application Ser.No. 09/581,952 and corresponding International (PCT) Publication No. WO99/32158. The most preferred amino biguanide is identified in U.S.patent application Ser. No. 09/581,952 as “Compound Number 1”. Thiscompound has the following structure:

[0039] It is referred to below by means of the code number “AL-8496”.

[0040] The ophthalmic compositions of the present invention willgenerally be formulated as sterile aqueous solutions. The compositionsmust be formulated so as to be compatible with ophthalmic tissues andcontact lens materials. The compositions will generally have anosmolality of from about 200 to about 400 milliosmoles/kilogram water(“mOsm/kg”) and a physiologically compatible pH.

[0041] The compositions of the present invention and the ability ofthose compositions to reduce protein adsorption on contact lenses arefurther illustrated by the following Examples. Unmodified (i.e.,non-ionic) NIPAM polymers and modified (i.e., end terminated with —COOHgroups) NIPAM polymers were added to appropriately buffered solutions todemonstrate the ability of these polymers to reduce protein adsorptionwhen utilized as components of buffered multi-purpose solutions fortreating contact lenses. A simple means of producing PNIPAM-modifiedsurfaces was used in order to mimic the contact lensdisinfection/cleaning regime typically used by the consumer.

EXAMPLE 1

[0042] The tests described below were conducted to evaluate the abilityof NIPAM polymers to modify contact lens surfaces and thereby reduceprotein adsorption.

[0043] Materials/Methods

[0044] The materials and methods utilized in the evaluation were asfollows:

[0045] Chemicals Lysozyme (Sigma, Chicken egg white, grade 1, 3×crystalline), Trifluoroacetic Acid Anhydrous (Sigma, Protein sequencinggrade) Acetonitrile (EM Science, HPLC grade), Sodium PhosphateMonobasic, Monohydrate (Sigma, ACS reagent grade), Sodium PhosphateDibasic, Anhydrous (Sigma, ACS reagent grade), Sodium Chloride (Sigma,ultra pure grade), Unisol®4 (Alcon Laboratories, Inc.,preservative-free. pH-balanced saline solution for rinsing)

[0046] The NIPAM polymers utilized are identified in Table 1 below.These polymers were purchased from Polymer Source Inc. and were usedwithout further purification. TABLE 1 Polymer Type M_(v) × 10³M_(w)/M_(n) P2991-NIPAM Non-ionic  46,380 2.36 P604-NIPAM Non-ionic 71,600 2.44 P1239-NIPAM Non-ionic 122,000 2.50 P2426F2-NIPAM- Anionic132,000 1.29 COOH

[0047] Lenses

[0048] Acuvue (Vistakon, a division of Johnson & Johnson VisionProducts, Inc) lenses were used as the substrate in this study. Thelenses had the following parameters: 42% etafilcon A, 58% water, FDAGroup IV lens. Diameter, 14.0 mm; base curve, 8.8 mm; power, −2.00.

[0049] Formulations

[0050] The NIPAM and NIPAM-COOH polymers identified in Table 1 wereformulated at pH 7.8 in a buffered vehicle containing 1.5% sorbitol,0.6% boric acid and 0.32% NaCl. In a beaker, all the formulationchemicals except for the NIPAM polymers were weighed out and purifiedwater was added (QS to 95%). The pH was adjusted to 7.8 with NaOH/HCl.The NIPAM polymer was weighed out and added to the buffer solution andthis was stirred overnight to solubilize the polymer. The testformulations are shown in Table 2 below; the concentrations areexpressed as weight/volume percent (“w/v%”): TABLE 2 Formulation Numbers9591-47C Component 9591-47A 9591-47B (Control) P2991-NIPAM 0.034 0.017 —Sorbitol 1.5 1.5 1.5 Boric Acid 0.6 0.6 0.6 Sodium Chloride 0.32 0.320.32 Purified Water QS QS QS pH 7.8 7.8 7.8

[0051] The test formulations were evaluated for their prophylaxisbehavior using lysozyme as the model protein, as described below.

[0052] Preparation of Deposition Solution

[0053] Phosphate Buffered Saline (PBS) 1.311 g of monobasic sodiumphosphate (monohydrate), 5.74 g of dibasic sodium phosphate (anhydrous),and 9.0 g of sodium chloride were dissolved in deionized water and thevolume was brought to 1000 mL with deionized water, and pH was adjusted(as necessary). The final concentrations of sodium phosphate and sodiumchloride were 0.05 M and 0.9%, respectively. The final pH was 7.4.

[0054] Lysozyme Solution

[0055] A 1.5-mg/mL lysozyme solution was prepared by dissolving 750 mgof lysozyme in 500-mL phosphate buffered saline pH adjusted to 7.4.

[0056] Lens Extraction Solution (ACNITFA)

[0057] A lens extraction solution was prepared by mixing 1.0 ml oftrifluoroacetic acid with 500-mL acetonitrile and 500 ml of deionizedwater. The pH of the solution ranged from 1.5 to 2.0.

[0058] Lens Presoak Procedure

[0059] Each lens was immersed in 3-mL of each test formulation andallowed to sit at room temperature overnight. The next morning, thelenses were removed from the test formulations and dabbed lightly on atowel.

[0060] Lens Deposition Procedure (Physiological Deposition Model)

[0061] Each presoaked lens was immersed in a Wheaton glass sample vialcontaining 3-mL of lysozyme solution. The vial was closed with a plasticsnap cap and incubated in a constant temperature water bath at 37° C.for 24 hours. Three additional lenses were included as controls toestablish the total amount of lysozyme deposited. After incubation, thedeposited lenses were removed from their vials and rinsed by dippinginto three consecutive beakers containing 200 ml Unisol®4 or water toremove any excess of the deposition solution.

[0062] Extraction and D t rmination of Lysozym Extraction

[0063] The lenses were extracted with 5 ml of ACN/TFA extractionsolution in a screw-capped glass scintillation vial. The extraction wasdone by shaking the vial with a rotary shaker (Red Rotor) at roomtemperature for at least 2 hours (usually overnight).

[0064] Calculations for the Determination of Lysozyme

[0065] Quantitative determination of the lysozyme of the lens extractwas carried out using a fluorescence spectrophotometer interfaced withan autosampler and a computer. The fluorescence intensity of a 2 mlaliquot from each sample solution was measured by setting theexcitation/emission wavelength at 280 nm/346 nm with excitation/emissionslits of 2.5 nm/10 nm, respectively, and the sensitivity of thephotomultiplier was set at 950 volts.

[0066] A lysozyme standard curve was established by diluting thelysozyme stock solution to concentrations ranging from 0 to 40 μg/ml,using the ACN/TFA extraction solution for the lens extract and thevehicle for the soaking solutions. The instrument settings for measuringthe fluorescence intensity were the same for the lens extracts and lenssoaking solutions.

[0067] The lysozyme concentrations for all of the samples werecalculated based on the slope developed from the linear lysozymestandard curve. The % prophylaxis of each formulation was calculated bysubtracting the amount of lysozyme in the lens extract from the amountof lysozyme from the control lenses (total deposit), then dividing thatby the total deposit and multiplying by 100.

[0068] Results

[0069]FIG. 1 shows the % prophylaxis as a function of PNIPAMconcentration (g/100 ml) for nonionic NIPAM polymers having molecularweights of 46,380; 71,600; and 122,000, respectively.

[0070]FIG. 1 shows that there was no significant PNIPAM molecular weightdependence on the % prophylaxis using the defined polymerconcentrations. PNIPAM concentrations up to 0.2 g/100 ml gave %prophylaxis results of approximately 30%. With increasing PNIPAMconcentrations above 0.2 g/100 ml the % prophylaxis could be increasedto 50% to 60% using polymer concentrations between 0.4 g/100 ml and 0.65g/100 ml. The % prophylaxis was not dependent is on the molecular weightof the NIPAM polymers.

EXAMPLE 2

[0071] The prophylactic properties of NIPAM polymers were furtherevaluated using a 3-day cycling study. Two sets of lenses were prepared.One set was presoaked in the formulations shown in Table 2 before goinginto the lysozyme solution, whereas the other set was not. Both sets oflenses were then placed in the lysozyme solution for 8 hours (Day 1). Atthe end of the day all the lenses were rinsed and put in theirrespective formulations to soak overnight. The following day (Day 2),the lenses went back into the lysozyme for the day (8 hours). This wasrepeated to complete 3 cycles (3 Days). At the end of the experiment allthe lenses were analyzed in accordance with the procedures described inExample 1. The results are presented in Table 3: TABLE 3 Uptake Amountof Lysozyme Removed Sample (ug/lens) sd (ug/lens) % Prophylaxis sd9591-47A(PS) 124.1 9.1 261.9 67.8 0.8 9591-47B(PS) 151.5 3.9 234.5 60.80.6 9591-47C(PS) 386.0 6.1 — — — 9591-47A 206.3 2.7 174.9 45.9 1.29591-47B 221.3 10.4 159.9 41.9 0.9 9591-47C 381.2 7.1 — — —

[0072] The results demonstrate that the buffered solutions containing aNIPAM polymer (i.e., P2991-NIPAM) were effective in reducing proteinuptake in both the presoaked and non-presoaked lenses. For example, thepresoaked lenses treated with solutions containing concentrations of0.034% and 0.017% of the NIPAM polymer demonstrated prophylaxis valuesof 67.8% and 60.8%, respectively. For the non-presoaked lenses theprophylaxis values were 45.9% and 41.9% at concentrations of 0.034% and0.017%, respectively.

[0073] The results set forth in Table 3 demonstrate that treatment ofthe lenses with a NIPAM polymer solution prior to exposure to proteinsis preferable. However, the results also show that even when the lenseshave already been exposed to proteins prior to an initial treatment witha NIPAM polymer solution, the uptake of protein is reduced when thelenses are subsequently treated with a NIPAM polymer solution. Thus, theresults of this study confirm that the compositions of the presentinvention are effective in reducing the formation of protein deposits oncontact lenses, even when the lenses are repeatedly exposed to proteincontamination.

EXAMPLE 3

[0074] The prophylaxis work was extended to formulations containing theantimicrobial agent AL-8496 with unmodified NIPAM (non-ionic) andmodified NIPAM (end functionalized with COOH) polymers. The formulationsevaluated are shown in Table 4, below: TABLE 4 Formulations forMicrobiology Evaluation of PNIPAM Formulations Containing A Contact LensDisinfecting Agent (AL-8496) Formulation Numbers 9591-44I Component9591-44B 9591-44C 9591-44D 9591-44E 9591-44F (Control) P2991-NIPAM 0.0870.21 P2426F2- 0.040 0.10 0.25 NIPAMCOOH AL-8496* 0.0004 0.0004 0.00040.0004 0.0004 0.0004 Tetronic ® 1304 0.1 0.1 0.1 0.1 0.1 0.1 Sorbitol0.4 0.4 0.4 0.4 0.4 0.4 Sodium borate 0.2 0.2 0.2 0.2 0.2 0.2 Sodiumcitrate 0.6 0.6 0.6 0.6 0.6 0.6 Propylene glycol 1.0 1.0 1.0 1.0 1.0 1.0Disodium edetate 0.05 0.05 0.05 0.05 0.05 0.05 pH 7.8 7.8 7.8 7.8 7.87.8 % Prophylaxis 37.4 ± 0.2 54.1 ± 1.0 51.0 ± 0.5 57.3 ± 0.4 62.8 ± 1.20.6 ± 0.0

[0075] The procedures utilized were the same as in Example 1. FIG. 2shows the prophylaxis data obtained using the overnight soak model withlenses pre-soaked in the respective PNIPAM formulations.

[0076]FIG. 2 shows that the prophylaxis properties of the NIPAM polymerswere retained in the presence of the antimicrobial agent AL-8496 andother formulation components, including cleaning ingredients (e.g.,citrate and Tetronic® 1304). The data demonstrate that both unmodifiedand modified NIPAM polymers can be incorporated into multi-purposecontact lens care formulations without compromising the prophylacticproperties of the polymers.

EXAMPLE 4

[0077] The disinfection activity of the formulations shown in Table 4above was also evaluated. The results are shown in Table 5 below. TABLE5 Disinfection Properties of PNIPAM Formulations containing AL-8496 Time9591- 9591- 9591- 9591- 9591- 9591- Microorganism (hrs) 44B 44C 44D 44E44F 44I Candida 6 2.8 3.0 3.0 3.4 3.2 3.0 albicans 24 3.9 4.5 6.0 6.05.3 6.0 Serratia 6 2.7 6.2 2.8 2.7 2.6 2.6 marcescens 24 5.5 6.2 5.5 6.25.5 4.9 Staphylococcus 6 5.5 4.5 5.5 4.4 4.3 4.9 aureus 24 6.2 5.0 6.26.2 6.2 5.2

[0078] The results demonstrate that the NIPAM polymers did not adverselyaffect the antimicrobial activity of the antimicrobial agent AL-8496.

EXAMPLE 5

[0079] Several formulations were evaluated to compare the prophylaxisproperties of PNIPAM with two well-known block co-polymers, Tetronic®1107 and Pluronic® F127. The formulation components and prophylaxisresults are given in Table 6, below.

[0080] The evaluation was carried out using the same procedures asoutlined in Example 1. The buffered solution utilized as a control(10581-85J) did not exhibit any prophylaxis properties. However, asshown in Table 6, the compositions of the present invention containingPNIPAM at concentrations of 0.2% (10581-85B) and 0.4% (10581-85C)produced prophylaxis results of 56.2% and 63%, respectively.

[0081] In contrast, the solutions containing Tetronic® 1107 andPluronic® F127 block co-polymers at concentrations of up to 0.8% did notproduce any significant prophylaxis. TABLE 6 10581- 10581- 10581- 10581-10581- 10581- 10581- Components 85B 85C 85E 85F 85H 85I 85J PNIPAM P29910.2 0.4 — — — — — Tetronic ® 1107 — — 0.4 0.8 — — — Pluronic ® F127 — —— — 0.4 0.8 — Sorbitol 1.5 1.5 1.5 1.5 1.5 1.5 1.5 Boric Acid 0.6 0.60.6 0.6 0.6 0.6 0.6 Sodium Chloride 0.32 0.32 0.32 0.32 0.32 0.32 0.32Purified Water QS QS QS QS QS QS QS pH 7.8 7.8 7.8 7.8 7.8 7.8 7.8 %Prophylaxis 56.2 + 0.1 63.0 + 0.4 0.00 + 2.3 4.1 + 2.2 0.0 + 2.1 0.0 +0.9 0.8 + 1.0

I claim:
 1. Use of NIPAM polymers to reduce protein adsorption on thesurfaces of medial devices.
 2. Use of NIPAM polymers to reduce proteinadsorption on the surfaces of contact lenses.
 3. A composition forreducing the formation of protein deposits on the surfaces of medicaldevices, comprising on effective amount of a NIPAM polymer.
 4. Acomposition according to claim 3, wherein the composition is adapted forthe treatment of contact lenses.